Event Year: 2005

Cristina is bothered by a new year's mandatory work limit. Izzie patient, Denny Duquette, wants two things: 1. a heart transplant, 2. Izzie. Addison detests Derek's trailer, Derek visits Meredith's mom, George treats a young teen hermaphrodite frustrated by her pre-pubescence. Other news includes patients doing uncanny things and relationship havoc being wrecked between the doctors, as per usual.

The holiday season has started but not everyone is in a festive mood. This is Alex's last day in the hospital unless he passes his boards practical exam the next day, thus everyone helps him to review so that he succeeds. However, Izzie is not happy about the others helping him and Meredith has to remind her of the true spirit of the Christmas holiday. Justin is in need of a new heart. One is available but he does not want it because he does not believe Santa gave it to him as his mother said. Cristina and Burke, both handling Justin's case, have opposing views on the matter due to their different stances on religion. Despite a reconciliation with his wife, Derek isn't in a festive mood. George has a simple case of a woman who has a bleeding ulcer, he realizes that the ulcer is caused by her entourage but fails to keep them away, with the consequence that it perforates.

Cristina Yang has little sympathy for Constance Ferguson (special guest star Rosanna Arquette), a prison inmate who jeopardizes her health just to get out of solitary confinement. Meanwhile the interns all keep careful watch on the family of premature quintuplets with a variety of serious health challenges, Izzie's anger at Alex reaches boiling point, and Dr. Addison Shepherd decides to teach Izzie a very painful lesson.

Dorie Russell is waiting for quintuplets, all 5 girls. Her husband seems more concerned than she is but she is set to bring her babies to their term of 36 weeks. All the departments are on call for the quintuplets as three of them have developped problems of different kinds. Meredith last night's stand shows up at the hospital with priapism and they need to call Derek Sheperd for a consult which puts Meredith in a very embarassing position. Alex and Derek must take care of a patient who has a tumor inducing thirst as a side effect. On the love side, Alex and Izzie are having some slight sexual problems, while Meredith goes on adding one night stands and Cristina is thrown off course by being "keyed."